Is IARS1 p.Phe49= (c.147T>C) pathogenic?

IARS1 p.Phe49= (c.147T>C) is classified Likely benign in IARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). Absent from gnomAD v4.1.

How common is IARS1 p.Phe49= (c.147T>C) in the general population?

IARS1 p.Phe49= (c.147T>C) is absent from gnomAD v4.1 (gnomAD).

IARS1 p.Phe49=

c.147T>C · VCV4779120

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.106	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.5, phastCons 1
Overall
CADD	11.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IARS1
Protein: p.Phe49=
Coding: c.147T>C
MANE Select: NM_002161
Type: single nucleotide variant
Location: chr9:92288255 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.06 · 1 PDB

Full IARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IARS1 p.Tyr71Ter Pathogenic ★★ same type
IARS1 p.Ala222Gly Uncertain significance ★★ ⚠ same type
IARS1 p.Ala325Thr Uncertain significance ★★ ⚠ same type
IARS1 p.Ala485Val Uncertain significance ★★ ⚠ same type
IARS1 p.Ala954Gly Uncertain significance ★★ ⚠ same type
IARS1 p.Ala954Ser Uncertain significance ★★ ⚠ same type
IARS1 p.Arg140Gln Uncertain significance ★★ ⚠ same type
IARS1 p.Arg511Cys Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/iars1-p-phe49 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown